Evidence map›Paper›PMID 40207431›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Early increase of the synaptic blood marker β-synuclein in asymptomatic autosomal dominant Alzheimer's disease.

Patrick Oeckl, Benjamin Mayer, Randall J Bateman, Gregory S Day, Nick C Fox, Edward D Huey, Laura Ibanez, Takeshi Ikeuchi, Mathias Jucker, Jae-Hong Lee and 11 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Changes in serum β-synuclein precede blood biomarkers of Alzheimer pathology in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  9. Early increase of the synaptic blood marker β-synuclein in asymptomatic autosomal dominant Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Patrick OecklDepartment of Neurology, Ulm University Hospital, Ulm, Germany.
Benjamin MayerInstitute for Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, Florida, USA.
Nick C FoxThe Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Edward D HueyDepartment of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Laura IbanezDepartment of Psychiatry, Department of Neurology, and NeuroGenomics and Informatics Center, Washington University, Saint Louis, Missouri, USA.
Takeshi IkeuchiBrain Research Institute, Niigata University, Niigata, Japan.
Mathias JuckerGerman Center for Neurodegenerative Diseases (DZNE) Tübingen, Tübingen, Germany.
Jae-Hong LeeDepartment of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Johannes LevinDepartment of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Jorge J Llibre-GuerraDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Francisco LoperaNeuroscience Group of Antioquia (GNA), Medicine Faculty, Antioquia University, Medellín, Colombia.
Eric McDadeDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
John C MorrisDepartment of Neurology and the Knight Alzheimer Disease Research Center, Washington University, Saint Louis, Missouri, USA.
Yoshiki NiimiUnit for Early and Exploratory Clinical Development, The University of Tokyo, Tokyo, Japan.
Jee Hoon RohDepartments of Neurology and Physiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
Raquel Sánchez-ValleAlzheimer's Disease and Other Cognitive Disorders Unit. Hospital Clínic de Barcelona, FRCB-IDIBAPS, University of Barcelona, Barcelona, Spain.
Peter R SchofieldNeuroscience Research Australia, Sydney, New South Wales, Australia.
Markus OttoDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.ORCID 0000-0003-4273-4267
Dominantly Inherited Alzheimer Network

Funding

Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
Alzheimer's Association SG-20-690363-DIANCure Alzheimer´s FundGerman Center for Neurodegenerative DiseasesKorea Health Technology R&D ProjectMinistry of Health & Welfare and Ministry of Science and ICT, Republic of Korea HI21C0066NIA NIH HHS U19 AG032438Raul Carrea Institute for Neurological ResearchResearch and Development Grants for Dementia from Japan Agency for Medical Research and Development AMED JP24dk0207066Spanish Institute of Health Carlos III
6 · The paper itself

Abstract

introductionβ-synuclein is a promising blood marker to track synaptic degeneration in Alzheimer's disease (AD) but changes in preclinical AD are unclear.

methodsWe investigated serum β-synuclein in 69 cognitively unimpaired mutation non-carriers, 78 cognitively unimpaired AD mutation carriers (asymptomatic AD), and 31 symptomatic mutation carriers from the Dominantly Inherited Alzheimer Network.

resultsβ-synuclein levels were already higher in asymptomatic AD mutation carriers compared to non-carriers and highest in symptomatic carriers. Longitudinal trajectories and correlation analyses indicated that β-synuclein levels start to rise after amyloid deposition preceding axonal degeneration, brain atrophy and hypometabolism, and cognitive decline. β-synuclein levels were associated with cognitive impairment and gradually increased with declining cognition. DISCUSSION: Our study supports the use of blood β-synuclein to track synaptic changes in preclinical AD and as a surrogate marker for cognitive impairment which might be used in early diagnosis and to support patient selection and monitoring of treatment effects in clinical trials. HIGHLIGHTS: Blood β-synuclein levels were already higher in asymptomatic Alzheimer's disease (AD) mutation carriers. Blood β-synuclein levels were highest in symptomatic AD mutation carriers. Blood β-synuclein levels start to rise 11 years before symptom onset. Rise of β-synuclein precedes axonal degeneration, brain atrophy, and cognitive decline. β-synuclein levels gradually increased with declining cognition.

Indexed as

Alzheimer Diseasebeta-SynucleinAgedBiomarkersBrainCognitive DysfunctionFemaleHumansLongitudinal StudiesMaleMiddle AgedMutationSynapsesbeta-SynucleinBiomarkersasymptomatic mutation carriersautosomal dominant Alzheimer´s diseaseblood biomarkerpreclinical Alzheimer´s diseasesynaptic degenerationβ‐synuclein

Identifiers

PMID40207431
PMCPMC11982912

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.